One significant issue with this link is that the severely mentally ill—the demographic most prescribed antipsychotics—have a higher risk of cardiovascular death than the general population, said Science Daily.
The new study utilized data from the multi-center CATIE (Clinical Antipsychotic Trials of Intervention Effectiveness) study, funded by the National Institute of Mental Health, said Science Daily. Jonathan Meyer and colleagues looked at a variety of antipsychotic medications’ effects on systemic inflammation and found the drugs increased “inflammation markers,” specifically, Zyprexa (generic: olanzapine) made by Eli Lilly and Co. and Seroquel (generic: quetiapine), made by AstraZeneca, said Science Daily.
Systemic inflammation, said Science Daily, has recently been found to be “an important marker” in cardiovascular risk; however, the link between antipsychotic medications and inflammatory markers was never looked at this deeply until now. Some of the markers are known to be linked to the “development or progression” of a variety of illnesses, namely stroke and cardiac disease, said Science Daily.
"This analysis provides the most compelling evidence to date that differences in antipsychotic metabolic liability are also seen with markers of systemic inflammation," explained Dr. Meyer, quoted Science Daily. "It also provides an impetus for monitoring cardiovascular risk markers in antipsychotic treated patients."
It has long been known and we have long written about the association between weight gain and antipsychotics and we recently wrote about another study that points to even deeper increases. In that study, researchers discovered that while increases in weight were dependent on the drug, the gains appeared in the entire spectrum of atypical antipsychotic medications, reported Forbes previously. The study found that weight gains of 10-to-20 pounds were not unusual in children during their first three months on the medications like Zyprexa, Seroquel, Risperdal, and Abilify. Also, cholesterol, triglyceride, and other metabolic “parameters” were elevated, said Forbes.
A serious issue with the findings is that children are being prescribed these powerful medications for diagnoses that are not psychotic in nature, such as aggression, sleep problems, and attention deficit disorder (ADD), noted Forbes. Experts feel these children would benefit from milder drugs and counseling. Another issue is a diagnosis that is growing in popularity. Pediatric bipolar disorder can be treated with atypical antipsychotics; however, diagnosis criteria is considered weak, reported Forbes.
The research found that children on Zyprexa gained 19 pounds in three months; children taking Seroquel, Johnson & Johnson’s Risperdal, and Bristol-Myers Squibb’s Abilify gained 10 to 13 pounds in the same time frame, said Forbes. Meanwhile, Seroquel and Zyprexa were linked to “statistically significant” cholesterol level increases and Seroquel, Zyprexa, and Risperdal were found to increase triglyceride levels, added Forbes, which explained that triglycerides are fatty particles in the blood.
A U.S. Food and Drug Administration’s (FDA) advisory panel voted to recommend approval of three popular psychotropic medications—atypical antipsychotics— for children with specific conditions. The vote concerned AstraZeneca PLC’s Seroquel Incendiary video , Eli Lilly and Company’s Zyprexa, and Pfizer Inc.’s Geodon .
According to the agency’s advisory panel, the three drugs have been deemed safe and effective for pediatric patients—children and teens—who have been diagnosed with schizophrenia or bipolar disorder, Reuters reported. However while the panel did recommend approval of the broader use for Seroquel, Zyprexa, and Geodon, it did warn about the drugs’ long-term effects in children, said Reuters. All three drugs are approved for use in adults and, like any other medication, can be used off-label if the prescribing physician feels the medication is warranted, in this case, to children, Reuters pointed out. An expanded approval by the FDA 48 Angels download would enable the industry to market the drugs for kids.
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The final approval decision rests with the FDA itself. The agency usually follows recommendations of advisory panels, though it is not required to do so.
Colour Me Kubrick: A True...ish Story movie Seroquel, Zyprexa, and Geodon have long been prescribed off-label to the younger demographic for schizophrenia and bi-polar diagnoses and many of these younger patients have connections to child welfare and juvenile justice systems, said Youth Today last week. For example, approximately 14 percent of children in foster care are prescribed some psychotropic medication, reported Youth Today citing a 2006 policy paper written by the Institute for Juvenile Research at the University of Illinois at Chicago. This figure will likely increase as the practice of prescribing atypical antipsychotics to children becomes a more greatly accepted practice, now that approval to do so has been granted.
But, the drugs are not without problems. For instance, this January, a study published in The New England Journal of Medicine found that patients taking Seroquel and other atypical antipsychotics were likelier to suffer sudden cardiac death than patients taking older antipsychotics. This April, an FDA advisory panel cited the risk of Seroquel and sudden cardiac death when it recommended the drug not be approved as a first line treatment for depression. AstraZeneca faces over 9,000 Seroquel lawsuits filed by people who claim the company withheld information about the drug’s diabetes risk.
In addition to blood sugar risks, there are concerns Geodon might increase the risk of a specific, potentially fatal heart-rhythm irregularity. Additional side effects include: Feeling unusually tired; nausea; constipation; dizziness; restlessness; diarrhea; rash; cough; runny nose; and abnormal muscle movements, including tremor, shuffling, and uncontrollable movements.
Some panel members expressed concern, said Reuters, that short-term research did not adequately reveal the effects of these medications on children over time. "I'm concerned about the lack of true long-term studies" especially in younger patients "who will have a long lifetime, hopefully," said Ruth Day, a researcher at Duke University, quoted Reuters. Some agency advisors were unclear why the FDA accepted the three medications in children for what would likely be a lifetime of treatment when studies only looked at this demographic for between three and six weeks, reported Reuters, noting that effect of these drugs on the developing brain remains unknown.
Also of concern was the likelihood of drug misuse and prescribing practices for other conditions—attention deficit disorder (ADD) or hyperactivity, to name two—Reuters pointed out, as well as treatment to much younger children. "Soon we'll be seeing four-, five- and six-year-olds being treated. It's a slippery slope ... I just get worried about where this is going," said Kenneth Towbin an agency panelist and head of the National Institute of Mental Health's child psychiatry mood disorders program, quoted Reuters.
Pirates of the Caribbean: Dead Man's Chest ripA vote is scheduled for next week regarding three psychotropic medications and their safety and efficacy for children with specific conditions. Youth Today reports that although the U.S. Food and Drug Administration (FDA) does not need committee approval for pharmaceutical company applications, the agency’s Psychopharmacologic Drugs Advisory Committee will be voting on Zyprexa, Seroquel
, and Geodon.
The Nine Lives of Fritz the Cat release While it is widely known that physicians have been prescribing Zyprexa, Seroquel, and Geodon to pediatric patients for some time, what might not be known is that many of those younger patients have connections to child welfare and juvenile justice systems, said Youth Today. For example, approximately 14 percent of children in foster care are prescribed some psychotropic medication, reported Youth Today citing a 2006 policy paper written by the Institute for Juvenile Research at the University of Illinois at Chicago.
The issue is rife with controversy because not only is the FDA not required to obtain approvals of this sort, many critics feel that there are too many so-called “troubled” children prescribed psychotropic medications, pointed out Youth Today.
Shortbus downloadAccording to David Cohen, a psychotherapist and professor at Florida International University, "When an advisory committee is convened, it usually means the evidence is not so clear," quoted Youth Today, which added that these types of committee rulings are sought in cases when "other issues need to be considered, or the consequences are so weighty," said Cohen.
Sharpe's Company dvdFor instance, in the case of Eli Lilly’s Zyprexa, prescribed "for the acute treatment of manic or mixed episodes associated with bipolar I disorder and the acute treatment of schizophrenia in adolescents," quoted Youth Today, there have been huge financial settlements linked to illegal marketing as well as significant adverse effects. Lilly agreed to pay the government $1.4 billion to settle criminal and civil cases, noted Youth Today. Zyprexa is known to cause significant weigh gain; diabetes, hyperglycemia, and other blood sugar disorders; lowering of good, or HDL, cholesterol levels; and cardiac issues.
AstroZeneca’s Seroquel is, quoted Youth Today, prescribed "for the acute treatment of schizophrenia in adolescents from 13 to 17 years of age, and the acute treatment of bipolar mania in children from 10 to 12 years of age and adolescents from 13 to 17 years of age." This January, a study published in The New England Journal of Medicine found that patients taking Seroquel and other atypical antipsychotics were more likely to suffer sudden cardiac death than patients taking older antipsychotic drugs. This April, an FDA advisory panel cited the risk of Seroquel sudden cardiac death when it recommended the drug not be approved as a first line treatment for depression. AstraZeneca faces over 9,000 Seroquel lawsuits filed by people who claim the company withheld information about the antipsychotic drug’s diabetes risk.
Slumdog Millionaire trailerPfizer’s Geodon is prescribed "for the acute treatment of manic or mixed episodes associated with bipolar disorder, with or without psychotic features in children and adolescents ages from 10 to 17 years of age." In addition to blood sugar risks, there are concerns Geodon might increase the possibility of a specific, potentially fatal heart-rhythm irregularity. Additional side effects include: Feeling unusually tired; nausea; constipation; dizziness; restlessness; diarrhea; rash; cough; runny nose; and abnormal muscle movements, including tremor, shuffling, and uncontrollable movements.
Lawyers for people suing Seroquel maker AstraZeneca will charge today that executives at the company discussed promoting the off-label use of the drug in children and elderly patients. According to The Wall Street Journal, the plaintiffs' attorneys will present documents that back up their claims at a news conference later today.
Seroquel - which was introduced in 1997 - is approved to treat psychotic disorders, schizophrenia and bipolar disorder. AstraZeneca faces over 9,000 Seroquel lawsuits filed by people who claim the company withheld information about the antipsychotic drug’s diabetes risk.
Off-label uses are those that have not been approved by the Food & Drug Administration (FDA). Doctors are permitted to use any approved drug in any way they see fit, but drug makers are legally barred from promoting off-label use.
According to The Wall Street Journal, there has been no evidence that off-label Seroquel use was promoted by AstraZeneca. But at today's news conference, attorneys will present evidence they claim show the company discussed doing so.
That evidence includes internal documents that cited plans to "broaden Seroquel use on and off-label," including among adolescents and patients with Parkinson's and Alzheimer's disease, at medical meetings, in sales calls and with patient-advocacy groups," the Journal said.
In one 2001 public relations plan reviewed by the Journal, one of the stated objectives was to "encourage and support" Seroquel's "use outside schizophrenia into a broad range of other patient populations including bipolar disorder and the elderly". The same document also said there was a need for "aggressive market penetration" among adolescents, the elderly, patients with bipolar disorder and other groups for Seroquel to grow faster than rivals, the Journal said.
Small Time Crooks ipod Atypical antipsychotics like Seroquel are favored by many doctors and patients because they carry a decreased risk of side effects related to loss of motor control, a major problem with older “typical” antipsychotics.
But Seroquel and similar drugs carry other safety risks. For instance, these drugs have long been linked to a risk of weight gain and diabetes, and in 2003, the FDA required the makers of atypical antipsychotics to re-label them to include warnings regarding their risk of hyperglycemia and diabetes mellitus. In 2005, the FDA also warned that such drugs increased the risk of death among elderly people.
According to The Wall Street Journal, an AstraZeneca official denied that any of the documents indicate a desire on the part of the company to promote off-label uses of Seroquel. Rather, the documents indicate the company's plan to "explore additional indications for Seroquel and included that in clinical-development plans designed to support efforts to investigate potential additional indications," the spokesperson said.
Seroquel was approved by the Food & Drug Administration Lock Up hd (FDA) in 1997 to treat schizophrenia. Atypical antipsychotics like Seroquel are favored by many doctors and patients because they carry a decreased risk of side effects related to loss of motor control, a major problem with older "typical" antipsychotics.
But Seroquel and similar drugs carry other safety risks. For instance, these drugs have long been linked to a risk of weight gain and diabetes, and in 2003, the FDA required the makers of atypical antipsychotics to relabel them to include warnings regarding their risk of hyperglycemia and diabetes mellitus. In 2005, the FDA also warned that such drugs increased the risk of death among elderly people.
In January 2009, the study on sudden cardiac death published in the NEJM raised even more concerns about Seroquel and other drugs in its class. For the study, scientists at the Vanderbilt University School of Medicine reviewed data on Tennessee Medicaid patients, comparing 44,218 people using older typical antipsychotics and 46,089 taking the newer atypical antipsychotics to 186,600 people who had never used the drugs.
Overall, people taking typical antipsychotics were at 1.99-times greater risk of sudden cardiac death, while the risk for those on atypical antipsychotics was increased 2.26 times. The increased risk was greater for people on higher doses of the drugs. People who had used the drugs in the past but stopped weren't at greater risk of sudden cardiac death. The researchers concluded that atypical antipsychotics are not a safer alternative to typical antipsychotics in preventing death from sudden cardiac causes.
The association between sudden cardiac death and Seroquel is especially disturbing given that it is frequently used off-label to treat elderly dementia patients, a group that already is more likely to suffer from heart problems.
Earlier this month, documents posted on the FDA website indicated that regulators were concerned about the association between Seroquel and sudden cardiac death. According to Reuters.com, the documents were released ahead of an FDA advisory panel meeting to consider expanding the approved uses of Seroquel XR (an extended release version of the drug) to include treatment of depression.
In one memo, the FDA's director of psychiatry drugs said cardiac effects still raise questions about the drug's safety. Other FDA documents noted the NEJM study, Reuters.com said.
The following week, the study was again cited when FDA advisers unanimously voted not to recommend that Seroquel be approved as a first-line treatment for depression. However, in a separate 6-to-3 vote, the panelists recommended that the medication could be used as supplemental treatment for patients with depression who do not get symptom relief from other drugs.
In a separate vote, said HealthDay News, citing the AP, the panel found that Seroquel could be taken as a supplement for depression—but not anxiety disorders—in those patients whose depression is not relieved from any other medications. The panel did not vote on the medication’s use in the treatment of anxiety disorders.
According to panel chairman, Dr. Wayne Goodman, who is also a psychiatric researcher at the U.S. National Institutes of Health (NIH), "I saw no clear advantage demonstrated in efficacy. There were side effects, and I would expect unintended consequences associated with wide-scale use of the drug," quoted HealthDay News.
Last week, the AP quoted FDA drug reviewer Thomas Laughren, in documents posted online as stating that, “There remains a concern about longer-term risks with this drug, in particular, risks related to metabolic changes.” The AP noted that Laughren was referring to a recent New England Journal of Medicine article concerning the link between an increase in sudden heart death and antipsychotic use.
Meanwhile, AstraZeneca apparently buried a Seroquel study completed the same year the drug was approved over concerns about the report’s disappointing results. According to an earlier report by The Washington Post, Seroquel Study 15 found that patients gained 11 pounds a year on the drug, something that would have put them at an increased risk of diabetes.
Seroquel was introduced in 1997 and has long been linked to a risk of weight gain and diabetes. Information on this risk was originally included in the “Adverse Reactions” section of its label. In 2003, the FDA required AstraZeneca to give the information added prominence by moving it to the label’s “Warnings” section. Earlier this year, the label was updated to include data on children and adolescents, including blood-glucose levels, cholesterol, weight gain, and increased appetite. Now, AstraZeneca faces over 9,000 Seroquel lawsuits filed by people who claim it withheld information about Seroquel’s diabetes risk. Several states that have also sued AstraZeneca have charged it illegally promoted Seroquel for unapproved uses.
In 1999, AstraZeneca touted different data at an American Psychiatric Association conference and at a European meeting. According to an earlier Washington Post article, AstraZeneca maintained this data showed that Seroquel helped psychotic patients lose weight. The company-funded study AstraZeneca used to back that claim was conducted by a Chicago psychiatrist, and internal documents reviewed by The Post indicate that AstraZeneca officials did not hold this doctor in high regard and had concerns he modified study protocols and failed to get informed consent from patients. They also wrote that they did not trust him with anything more complicated than chart reviews, the Post said.
The AP said that Seroquel XR is taken by millions of patients for schizophrenia and bipolar disorder, but that AstraZeneca is hoping the FDA will approve the drug for depression and anxiety disorder, which accounts for an additional 20 million Americans. In response, the FDA is asking an external panel to look at the drug’s side effects, including weight gain and tics, said the AP.
The Wall Street Journal reported that the external panel will conduct its review of the extended release medication on April 8 and that the FDA said the review will look at "concerns regarding exposing a greatly expanded population to a drug with known metabolic side effects and a possible risk of tardive dyskinesia." Tardive dyskinesia is a neurologic disorder.
"There remains a concern about longer-term risks with this drug, in particular, risks related to metabolic changes," said FDA drug reviewer Thomas Laughren, in documents posted online, quoted the AP. The AP noted that Laughren referred to a recent New England Journal of Medicine article concerning the link between an increase in sudden heart death and antipsychotic use, and if Seroquel has "been shown to be acceptably safe for the treatment" of depression and anxiety, said the AP.
Meanwhile, AstraZeneca apparently buried a Seroquel study completed the same year the drug was approved over concerns about the report’s disappointing results. According to an earlier report by The Washington Post, Seroquel Study 15 found that patients gained 11 pounds a year on the drug, something that would have put them at an increased risk of diabetes.
Seroquel was introduced in 1997 and has long been linked to a risk of weight gain and diabetes. Information on this risk was originally included in the “Adverse Reactions” section of its label. In 2003, the FDA required AstraZeneca to give the information added prominence by moving it to the label’s “Warnings” section. Earlier this year, the label was updated to include data on children and adolescents, including blood-glucose levels, cholesterol, weight gain, and increased appetite.
Now, AstraZeneca faces over 9,000 Seroquel lawsuits filed by people who claim it withheld information about Seroquel’s diabetes risk. Several states that have also sued AstraZeneca have charged it illegally promoted Seroquel for unapproved uses.
In 1999, AstraZeneca touted different data at an American Psychiatric Association conference and at a European meeting. According to an earlier Washington Post article, AstraZeneca maintained this data showed that Seroquel helped psychotic patients lose weight. The company-funded study AstraZeneca used to back that claim was conducted by a Chicago psychiatrist and internal documents reviewed by The Post indicate that AstraZeneca officials did not hold this doctor in high regard and had concerns he modified study protocols and failed to get informed consent from patients. They also wrote that they did not trust him with anything more complicated than chart reviews, the Post said.
Seroquel - which was introduced in 1997 - has long been linked to a risk of weight gain and diabetes. Information on this risk was originally included in the “Adverse Reactions” section of its label. In 2003, the Food & Drug Administration (FDA) required AstraZeneca to give the information added prominence by moving it to the label’s “Warnings” section. Earlier this year, the label was updated to include data on children and adolescents, including blood-glucose levels, cholesterol, weight gain and increased appetite.
AstaZeneca faces over 9,000 Seroquel lawsuits filed by people who claim the company withheld information about the antipsychotic drug’s diabetes risk. Several states that have also sued AstraZeneca have charged that the company illegally promoted Seroquel for unapproved uses.
The saga of Seroquel Study 15 was uncovered in the course of this litigation. According to The Washington Post, the weight gain seen in the study alarmed AstraZeneca. Company emails unsealed in Seroquel lawsuits indicate that AstraZeneca executives endorsed a company doctor's efforts to put a "positive spin" on Study 15. Company officials also discussed misleading doctors by "cherry-picking" data.
According to The Washington Post, Study 15 - which compared patients taking varying doses of Seroquel to those taking the older drug Haldol - also should have raised serious questions about Seroquel's effectiveness. The study showed that Seroquel failed to outperform Haldol in preventing psychotic relapses. The makers of atypical antipsychotics like Seroquel have long maintained they work better than older generation drugs.
In 1999, AstraZeneca touted different data at an American Psychiatric Association conference and at a European meeting. According to The Post, the company maintained that this data showed that Seroquel helped psychotic patients lose weight.
The company-funded study AstraZeneca used to back that claim was conducted by a Chicago psychiatrist. This doctor reviewed the records of 65 patients who switched their medication to Seroquel, the Post said. He concluded that patients lost an average of nine pounds over 10 months. But other internal documents reviewed by the Post indicate that AstraZeneca officials did not hold this doctor in high regard. They had concerns that he had modified study protocols and failed to get informed consent from patients. They also wrote that they did not trust him with anything more complicated than chart reviews, the Post said.
While the public never got to see Seroquel Study 15, the FDA did - yet it approved the drug anyway. According to the Post, the FDA claims it did not have the authority to make Study 15 public.
As a result, eight years later when a taxpayer-funded study on the effectiveness of Seroquel and other atypical antipsychotics reached conclusions similar to those in Study 15, patients who had been taking Seroquel, as well as doctors who prescribed it, were taken by surprise. One psychiatrist interviewed by the Post said that had doctors known about Seroquel Study 15 in 1997, "it would raise your eyebrows."
Seroquel - which was introduced in 1997 - has long been linked to a risk of weight gain and diabetes. Information on this risk was originally included in the “Adverse Reactions” section of its label. In 2003, the FDA required AstraZeneca to give the information added prominence by moving it to the label’s “Warnings” section. Then in January, the label was updated to include data on children and adolescents, including blood-glucose levels, cholesterol, weight gain and increased appetite.
AstraZeneca faces over 9,000 Seroquel lawsuits filed by more than 15,000 people who claim the company withheld information about the drug’s diabetes risk. As we've previously reported, other documents unsealed in the course of litigation appear to support these claims. For example, a February 1997 e-mail from an AstraZeneca official that was revealed last month said that the company had engaged in a “great smoke-and-mirrors job” in dealing with U.S. and Canadian investigators regarding a trial that didn’t produce favorable results on the issue of weight gain and Seroquel.
In a December 1999 email, the company’s publication manager wrote that AstraZeneca “buried” disappointing results from three clinical trials. The same email also faulted AstraZeneca for having “cherry picked” data from one of those studies for use in a presentation.
Additional documents unsealed this month included some related to an AstraZeneca’s efficacy analysis, The analysis, which was produced in 2000, involved a dozen different Seroquel studies. According to The Wall Street Journal, the analysis concluded that Seroquel did not work as well haloperidol, a 50 year old generic drug. Even so, a slide from 2003 AstraZeneca PowerPoint presentation directly contradicted the analysis’ findings by stating: “Head to head with haloperidol, Seroquel offers the same — or better — efficacy and the added advantage of a significantly better clinical response.”
According to the Associated Press, the Seroquel plaintiff is seeking to have an additional 19 documents unsealed. His lawyers have asked New Jersey Superior Court Judge Jamie Happas to unseal the papers so they may be presented at the FDA's April advisory panel meeting.
"We think it's important that they have the benefit of what we have learned," one of the plaintiff's attorneys told The Associated Press. "What we believe the FDA does not have are internal memos where they analyze the studies (and state) their real opinions or concerns about the data."
At the April 8 meeting, the FDA panel will consider expanding the approved uses of Seroquel XR to include the treatment of depression and anxiety. Seroquel XR was approved in May 2007 for treating schizophrenia in adults and approved in October 2008 for use in patients with bipolar disorder, the Associated Press said.
AstraZeneca faces over 9,000 Seroquel lawsuits filed by people who claim the company withheld information about the drug’s diabetes risk. Several states that have also sued AstraZeneca have charged that the company illegally promoted Seroquel for unapproved uses. As we reported previously, documents unsealed in the course of litigation appear to back up these claims.
Additional documents, including those related to AstraZeneca's efficacy analysis, were unsealed last Friday as part of the litigation, the Journal said. The analysis, which was produced in 2000, involved a dozen different Seroquel studies. According to The Wall Street Journal, the analysis concluded that Seroquel did not work as well haloperidol, a 50 year old generic drug.
Even so, a slide from 2003 AstraZeneca PowerPoint presentation directly contradicted the analysis' findings by stating: "Head to head with haloperidol, Seroquel offers the same -- or better -- efficacy and the added advantage of a significantly better clinical response."
Other documents indicate that doctors at AstraZeneca debated how the analysis should be handled, the Journal said
Last week, Bloomberg.com detailed other unsealed documents that seemed to indicate that AstraZeneca tried to hide information that confirmed a link between Seroquel and diabetes. These included a February 1997 e-mail from an AstraZeneca official said that the company had engaged in a “great smoke-and-mirrors job” in dealing with U.S. and Canadian investigators regarding a trial that didn’t produce favorable results on the issue of weight gain and Seroquel.
In a December 1999 email, the company’s publication manager wrote that AstraZeneca “buried” disappointing results on weight gain and diabetes from three clinical trials. The same email also faulted AstraZeneca for having “cherry picked” data from one of those studies for use in a presentation, Bloomberg said.
According to The Wall Street Journal, documents among those unsealed Friday also indicated that AstraZeneca was not forthcoming about Seroquel, weight gain and diabetes. According to one document, the company used a case study involving a single Seroquel patient who lost weight to promote the drug. But a company email indicated that the link between Seroquel and the patient's weight loss was overstated.
According to The Wall Street Journal, Seroquel - which was introduced in 1997 - has long been linked to a risk of weight gain and diabetes. Information on this risk was originally included in the "Adverse Reactions" section of its label. In 2003, the Food & Drug Administration (FDA) required AstraZeneca to give the information added prominence by moving it to the label's "Warnings" section. Then last month, the label was updated to include data on children and adolescents, including blood-glucose levels, cholesterol, weight gain and increased appetite, the Journal said.
According to Bloomberg.com, AstaZeneca faces over 9,000 Seroquel lawsuits filed by people who claim the company withheld information about the drug's diabetes risk. Several states that have also sued AstraZenaca have charged that the company illegally promoted Seroquel for unapproved uses.
Documents unsealed in the course of litigation appear to back up these claims. According to Bloomberg.com, a February 1997 e-mail from an AstraZeneca official said that the company had engaged in a “great smoke-and-mirrors job” in dealing with U.S. and Canadian investigators regarding a trial that didn’t produce favorable results on the issue of weight gain and Seroquel.
In a December 1999 email, the company's publication manager wrote that AstraZeneca "buried" disappointing results from three clinical trials. The same email also faulted AstraZeneca for having "cherry picked" data from one of those studies for use in a presentation, Bloomberg said.
The Wall Street Journal report details a transcript from a 2005 voicemail to AstraZeneca sales reps in which a company employee says the reps should address doctors' fears about their patients' weight gains by telling them that data showed no causal link between diabetes and the drug. According to the Journal, that email may have contradicted a 2000 position paper about the safety of Seroquel sent to Dutch regulatory authorities. In that paper, an AstraZeneca doctor wrote that there was a relationship between the drug and diabetes.
A company spokesperson told the journal that the position paper did not "accurately reflect its position", that the paper was "an initial draft for discussion purposes", and that the doctor who wrote it ultimately "concluded the evidence did not establish that Seroquel causes diabetes."
The first Seroquel lawsuit is scheduled to go to trial in April. Other atypical antipsychotic have also been linked to diabetes. According to Bloomberg, Zyprexra-maker Eli Lilly as agreed to pay at least $1.2 billion to similar settle lawsuits filed by about 31,000 patients.
Atypical antipsychotics, among the best-selling in the world, are used to treat schizophrenia and other mental problems. But according to Reuters, they are also widely used off-label to treat dementia and childhood hyperactivity. Many experts and patient advocates have called for a halt to such practices, and this study will likely add ammunition to their arguments.
For this latest study, researchers at the University of Vanderbilt studied nearly 277,000 people in Tennessee. About 46,000 were taking atypical antipsychotic drugs and 44,000 were taking typical antipsychotic drugs. About 187,000 weren't taking any of the drugs. Patients ranged in age from 30 to 74 years; the average age was about 46.
The study found that those taking the highest dose of the new antipsychotics had the greatest risk of heart failure and death, Reuters said. The danger faded once they stopped taking the drugs. The risk spanned all age groups, including younger people.
The drugs studied in this group included clozapine, made generically, Johnson & Johnson's Risperdal, Zyprexa, and Seroquel, made by AstraZeneca, Reuters said. The "typical" drugs used for comparison were haloperidol and thioridazine, both generics.
According to The Wall Street Journal, an editorial accompanying the study said the use of such drugs should be "reduced sharply" among children and elderly patients
Last week, we reported that another study conducted by scientists at the Wolfson Centre for Age-Related Diseases at King’s College London found that use of antipsychotic drugs to treat Alzheimer's disease patients doubled their chance of dying. While they are not approved for that use, antipsychotics are used in dementia patients, including those with Alzheimer's to control dementia. Researchers conducting the British study concluded that the risks of the drugs in these patients outweighed any potential benefits.
According to Reuters, in June the U.S. Food and Drug Administration (FDA) said older, conventional antipsychotic medications should carry a warning on the packaging about the risk of death. The FDA issued a similar warning in 2005 for newer antipsychotics.
In a letter to AstraZeneca released yesterday, the U.S. Food and Drug Administration (FDA) said in January a company sales representative told a doctor that Seroquel was approved for treating depression. The physician asked for related information and AstraZeneca sent a mailing summarizing research studies of Seroquel in depression. Seroquel and Seroquel XR are not approved for treating depression, notes Reuters. "The representative and the mailing recommended or suggested a use for Seroquel and Seroquel XR that has not been approved by FDA, and thus created a new 'intended use' ... for which the products lack adequate directions," the FDA letter said.
Seroquel, known generically as quetiapine fumarate, was approved by the FDA in 1997 and is prescribed for use two or three times a day by mouth to control the psychotic symptoms of bi-polar disorder and schizophrenia. Seroquel is also sometimes used "off-label" to treat unapproved conditions, including dementia, autism, and psychotic depression.
Doctors are free to prescribe approved medications off-label, but drug makers are not allowed to promote such uses.
Reuters reported that the FDA letter indicated that while the AstraZeneca mailing said it did not recommend Seroquel for off-label uses, its disclaimer was "insufficient to mitigate the promotion" of a new use. The FDA has asked AstraZeneca to cease using any similar promotional material, Reuters said.
AstraZeneca and Seroquel have long been the focus of controversy, For instance, on August 22, 2003, The Wall Street Journal published an article detailing an abstract from a study on atypical antipsychotic medications, including Seroquel that indicated that people taking these drugs were more likely to develop diabetes than patients taking older medications. In January 2004, the FDA asked AstraZeneca to include warnings about the risk of hyperglycemia (high blood sugar) and diabetes associated with the use of Seroquel. The FDA said that in some cases, hyperglycemia has resolved when these drugs were discontinued; however, some patients required continuation of anti-diabetic treatment despite discontinuation of the suspect drug.
In 2006, the FDA warned that Seroquel and other atypical antipsychotics had been associated with an increased risk of death when used to treat dementia. Seroquel was never approved to treat dementia, and this constitutes another "off-label" use of the drug.
In November 2006, the FDA issued AstraZeneca a warning letter alleging that some of the company’s promotional material for Seroquel contained “false or misleading” information. According to the FDA, AstraZeneca failed to adequately detail the risks of hyperglycemia and diabetes and omitted important data about neuroleptic malignant syndrome and other relevant conditions associated with Seroquel. The promotional piece mentioned in the letter was a fact sheet about Seroquel distributed to doctors along with the drug's FDA-approved product label.
Drugs receive US Food and Drug Administration (FDA) approval for specific purposes; however, medications are often prescribed as off-label—purposes other than that for which they were approved—on some difficult-to-treat conditions. Off-label prescribing is legal at physician discretion; however, off-label marketing by drug companies is in violation of federal law.
The first antipsychotics, like Thorazine, helped many but came with severe side effects, such as tardive dyskinesia, involuntary and debilitating movements. The second generation, dubbed atypicals, emerged in the 1990s and cause fewer involuntary movements, but weight gain and diabetes can result from their use, said Tom Clark, clinical affairs director for the American Society of Consultant Pharmacists Foundation. Atypicals include Risperdal, made by Janssen Pharmaceutica, part of Johnson & Johnson; Zyprexa from Eli Lilly & Co.; Seroquel by AstraZeneca P.L.C.; Geodon by Pfizer Inc.; and Abilify by Bristol-Myers Squibb Co.
State officials are finding atypicals have become the largest drug class in Medicaid and many question if this is due to illegal off-label marketing or true patient need. Several states are suing drug makers for off-label promotion and commissioning "ghost-written" articles to increase use of their products. Meanwhile, drug makers are obtaining new approvals from the FDA to treat more conditions. For instance, in the last two years, Risperdal received approval to treat schizophrenia in adolescents and the irritability of autism in children ages five to 16.
However, increased use of these new antipsychotics can have unforeseen results. Nicola Huff, whose son, John Aaron, took Risperdal for seven years to resolve behavioral problems said at age 14, he developed female-sized breasts that had to be surgically removed. Tammy Wandling, whose son Austin has autism, said a psychiatrist put him on Risperdal at age four. In less than nine months, Austin developed a baseball-size growth in his right breast. Research suggests Risperdal can cause an increase in the hormone prolactin, which causes breasts to enlarge and make milk.
More than 26 percent of the nation's nursing home residents were on antipsychotics in early 2007, compared with 19.4 percent in 1999, federal surveys show. Those drugs do little to help dementia patients, said Lon S. Schneider, a California psychiatrist and lead investigator of the CATIE-AD study of outpatients with Alzheimer's. He and his colleagues found that patients on anti-psychotics for 12 weeks had a slightly greater risk of dying sooner than those on placebo.
Zyprexa-maker Lilly set aside $1.2 billion to settle 31,000 claims and still faces 1,200 cases and a federal probe. Bristol-Myers Squibb, maker of Abilify, agreed to pay $515 million last year, in part to settle off-label marketing allegations; the firms also face thousands of additional claims. AstraZeneca has 8,000 suits pending for Seroquel.
In 2005, Medicaid spent $5.4 billion on atypical antipsychotic medicines—more than it spent on any other drug class, including antibiotics, AIDS drugs, or high blood pressure. Atypical antipsychotics are approved for schizophrenia and bipolar disorder, but in what is known as "off label" use—use not approved by the FDA for FDA-approved medications—doctors often prescribe the drugs to dementia patients. The widespread use of antipsychotics among the elderly has begun to draw criticism from regulators, researchers, lawmakers, and the nursing-home industry. Senator Charles Grassley, the ranking Republican on the Senate Finance Committee, asked several drug manufacturers for records on how they may have marketed these drugs for use in geriatric patients and also has asked the Inspector General of the Department of Health and Human Services to investigate use of the drugs in nursing homes.
The $122 billion nursing-home industry has moved toward large, often understaffed, institutions where use of psychotropic drugs is rising. According to CMS, nearly 21% of nursing-home patients who don't have a psychosis diagnosis are on antipsychotics. A 2005 study found antipsychotics were prescribed not only for psychosis, but for depression, confusion, memory loss, and feelings of isolation. Last year, CMS instituted new guidelines to limit the use of antipsychotics; however, it's still easier for nursing homes to get reimbursed for giving patients extra pills than it is for hiring extra staff.
An Alzheimer's patient often cannot refuse antipsychotic drugs, says Cynthia Rudder, of the Long-Term Care Community Coalition. "You are basically quieting them against their will and it is absolutely horrendous," she says. Family members can object to the use of such drugs, but risk having their relative discharged for unruly behavior.
At CMS, officials stress the need to shift to smaller, less-rigid facilities as a way to reduce antipsychotic usage. Some nursing-home-industry officials agree change is needed, yet replacing drugs with approaches that require a more human touch is easier said than done.
There are some Alzheimer's patients for whom nonpharmacological approaches simply don't work, says William Thies, a vice president at the Alzheimer's Association in Chicago, and in these cases antipsychotics may be warranted. But the drugs need to be used very carefully, at the lowest dose and after ruling out a medical problem, says Thies, who has a doctorate in pharmacology.
A spokesman for AstraZeneca Pharmaceuticals LP, maker of Seroquel, says "decisions about medical treatment are made by physicians" and the company doesn't recommend the drug "for uses other than its approved indications in schizophrenia and bipolar disorder."
But according to the Wall Street Journal, some pharmaceutical companies have attracted scrutiny for marketing drugs for unapproved uses. It is illegal for drug makers to promote off-label uses, but doctors may prescribe medications as they see fit. Last month, the Arkansas attorney general filed suit against Johnson & Johnson and two of its units, claiming, among other things, that they "engaged in a false and misleading campaign" to promote its antipsychotic drug Risperdal to geriatric patients.
A new report published in the current issue of the Canadian Medical Association Journal (CMAJ) claims that, among elderly patients, €œthe risk of death associated with conventional antipsychotic medications is comparable to and possibly greater than the risk of death associated with atypical antipsychotic medications. Until further evidence is available, physicians should consider all antipsychotic medications to be equally risky in elderly patients. €
Researchers studied more than 37,000 seniors and discovered that, within the first 180 days of treatment, 14.1 percent of the conventional-drug group died, compared to 9.6 percent of the atypical-drug group. Patients taking high dosages of conventional drugs faced a 67 percent increase in mortality. In addition, the study found that patients who had taken a conventional medication had a 32 percent greater (dose-dependent) risk of death within 180 days than those who were given an atypical agent.
In 2005, Health Canada, the government €™s public-health watchdog, reported that atypical antipsychotic medications increased the risk of death by 60 percent in trials involving elderly patients with dementia. However, researchers were concerned that warnings about the new atypical antipsychotic drugs were causing physicians to prescribe conventional antipsychotic treatments more frequently even though their overall safety has not been proven either.
The authors of the study believe that regulatory product warnings should be expanded to account for these new findings. €œThe results from our study strongly suggest that Health Canada and the FDA should include conventional antipsychotic medications in their public health advisories, which currently warn only of the increased risk of death associated with the use of atypical antipsychotic medications in elderly patients with dementia. €
They also note, €œAntipsychotic medications are disproportionately used in elderly populations and have been prescribed to over a quarter of U.S. Medicare beneficiaries in nursing homes € and that €œmuch use is outside approved indications. €
The FDA sent its warning letter on November 16 to James Gaskill, AstraZeneca €™s director of promotional regulatory affairs. The letter held the company in violation of the Federal Food, Drug, and Cosmetic Act because of a misleading promotional sales aid for Seroquel. The promotional material does not include significant data from the product €™s required patient-information labeling. According to the FDA €™s letter, €œThe promotional material raises significant public health and safety concerns through its minimization of the risks associated with Seroquel. €
The FDA is asking AstraZeneca to refrain from circulating the misleading materials. The company has until the end of the month to respond to the warning letter, but has announced its intentions to work with the FDA to resolve the matter.
Last week, the company announced a 30 percent gain in third-quarter net profit to $1.59 billion, attributing its success in part to expanded use of Seroquel for the treatment of manic bipolar disorder. In 2005, sales of Seroquel totaled about $2.76 billion. Earlier this month, the FDA officially approved the drug for the treatment of bipolar depression. It had already been approved for schizophrenia, and now it is the only drug approved for both depressive and manic bipolar behavior. Seroquel and Nexium, an ulcer drug, account for more than half of AstraZeneca €™s sales.
The reasons for the subpoenas are unclear at this time. Recently, studies have questioned the effectiveness of Seroquel in the treatment of various ailments. A new study published in the New England Journal of Medicine found €œno significant differences € between the effectiveness of atypical antipsychotic drugs and that of placebos in the treatment of Alzheimer €™s patients who suffer from psychosis, aggression, and agitation. Since Seroquel and other atypical antipsychotics often come with dangerous side effects, researchers questioned whether they should be used at all for Alzheimer €™s patients.
Only the week before the NEJM study, a study published in the Archives of General Psychology and funded by the British National Health Service found that costly second-generation antipsychotic drugs such as Seroquel and Zyprexa are no more effective than older, cheaper drugs in the treatment of schizophrenia. Many medical professionals pointed to aggressive marketing tactics by AstraZeneca and other drug producers as one of the reasons why atypical or second-generation antipsychotics command such a large market share.